Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Terminated; Phase 2

Conditions: Kidney Transplant Recipients

Treatments: Drug: Tacrolimus (CNI) Withdrawal; Drug: Standard Immunosuppressive Therapy

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT01517984

DAIT CTOT-09

Details and patient eligibility

About

The study will compare how well transplanted kidneys work and the response of people's immune systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn. In addition, this research study will evaluate whether reducing immunosuppression can decrease some of these side effects while still preventing rejection of the kidney.

Full description

Kidney transplantation is a treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it functioning for a long time. Transplant recipients take immunosuppression (anti-rejection) drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent the immune system from attacking the transplanted kidney. All anti-rejection medications have unwanted side effects. The purpose of this study is to evaluate the safety of slowly removing tacrolimus, a CNI.

Enrollment: 52 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA -

Initial Enrollment/Screening: Patients who meet all of the following criteria are eligible for enrollment as study subjects:

• Subject must be able to understand and provide written informed consent;
• Primary living-donor (related or unrelated) kidney transplant recipients;
• Peak flow-based PRAs for class I and class II <30%(performed by local center);
• Current (within 8 weeks prior to transplantation) flow-based PRAs for class I and class II <30% (performed by local center);
• No donor specific antibody by flow solid phase method on the peak PRA serum (if serum available), or on the current PRA serum (within 8 weeks prior to transplantation) performed by central core laboratory. If the sera for the peak PRA is not available, then only the current PRA serum will be tested;
• Negative T-cell and B-cell crossmatch by flow cytometry (performed by local center);
• Female subjects of childbearing potential must have a negative pregnancy test (urine or serum) upon study entry;
• Female and male subjects with reproductive potential must agree to use FDA approved methods of birth control while participating in the study.

Inclusion Criteria for Randomization:

Participants who meet all of the following criteria are eligible for randomization:

• No history of acute rejection episodes;
• The pre-randomization protocol biopsy should confirm no rejection, including borderline rejection (based on the central pathology read);
• No donor specific antibody as detected by flow solid phase method (performed by the central core laboratory).

EXCLUSION CRITERIA -

Initial Enrollment/Screening:

Participants who meet any of these criteria are not eligible for enrollment as study subjects:

• Recipient of multiple organ transplants;
• Prior history of organ transplantation;
• Deceased-donor source;
• Any condition that would preclude protocol biopsies;
• HLA identical recipients;
• Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;
• Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
• Inability or unwillingness to comply with study protocol;
• Use of investigational drugs within 4 weeks of study entry and for the duration of the study;
• Recent recipient of any licensed or investigational live attenuated vaccine(s) within two months of prior to study entry.

Exclusion Criteria for Randomization:

Participants who meet any of these criteria are not eligible for randomization:

• Subjects who receive less than 4.5mg/kg of Rabbit ATG (Thymoglobulin®) induction therapy;
• Subjects who test positive for BKV by PCR in the blood at 6 months post-transplant;
• Any condition that would preclude protocol biopsies;
• Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;
• Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
• Inability or unwillingness of a subject to give written informed consent or comply with study protocol;
• Use of investigational drugs within 4 weeks of study entry and for the duration of the study;
• Subjects who receive less than 1500 mg daily of Mycophenolate Mofetil (CellCept®) or equivalent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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52 participants in 2 patient groups

Tacrolimus (CNI) Withdrawal

Experimental group

Description:

Subjects randomized (2:1) to tacrolimus (CNI) withdrawal. Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.Subjects without any clinical acute rejection (AR) in the first 6 months, without borderline or acute rejection on the 6 month biopsy, and without donor-specific antibody (DSA) at anytime, including the 6 month test are randomized (2:1) to tacrolimus (CNI) withdrawal.

Treatment:

Drug: Standard Immunosuppressive Therapy

Drug: Tacrolimus (CNI) Withdrawal

Standard Immunosuppressive Therapy

Active Comparator group

Description:

Subjects randomized to standard immunosuppressive therapy, without subsequent tacrolimus (CNI) withdrawal. Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus. Tacrolimus (CNI) withdrawal does not occur.

Treatment:

Drug: Standard Immunosuppressive Therapy